The long-range purpose of this project is initially to study the immunologic aspects of the factor VIII/von Willebrand factor protein, and then to study the biochemistry and structure of this protein in man. The topics of the present interest are: 1) the defect of the factor VIII/von Willebrand factor protein in hemophilia A; 2) the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease; 3) the importance of carbohydrate content in biological functions; 4) the relationship of carbohydrate content to atherosclerosis; 5) the mechanism of thrombin activation, and 6) biochemical characterization of the biologically active sites of the factor VIII/von Willebrand factor protein. Recent studies of the platelet von Willebrand factor isolated from human platelets reveal significant differences from its plasma counterpart. Studies of better purification methods will allow for greater yields which, in turn, will allow biochemical characterization of the platelet von Willebrand factor.